Search Results (93)

Hereditary breast cancer (BC) remains unexplained in a substantial proportion of families who test negative for BRCA1/2 and other known susceptibility genes. To contribute to the genomic characterization of these unresolved cases, we generated a whole-genome sequencing (WGS) dataset from six women belonging to two unrelated high-risk families, each comprising three sisters diagnosed with BC. All participants had previously received negative results in conventional multigene panel testing. WGS was performed on peripheral blood DNA using the Illumina NovaSeq platform, followed by variant calling against GRCh38 and the comprehensive annotation of single-nucleotide variants, indels, and structural variants. For each family, we identified shared ClinVar-annotated variants, rare exonic or splice-site alterations, and intronic variants located within a curated set of 286 cancer-related genes. The dataset includes per-patient VCF files, copy number variation annotations, and family-level variant summaries. Raw and processed data are publicly available through the Sequence Read Archive and Zenodo. This resource supports variant reinterpretation, exploration of regulatory and intronic regions, and methodological benchmarking in the study of familial BC beyond established susceptibility genes. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) provides improved pain response and local control for spinal metastases. However, management of local failure after initial SBRT is challenging. We report institutional outcomes, dosimetry, and toxicity for reSBRT following SBRT. Methods: We retrospectively reviewed 61 lesions (55 patients) treated with reSBRT after prior SBRT. Both SBRT courses delivered a median dose of 27 Gy. Patients underwent clinical and radiological evaluation every three months. Toxicity was graded using CTCAE v5.0. Dosimetric parameters for the spinal cord (SC), cauda equina (CE), planning organ-at-risk volumes (PRV), and thecal sac were converted to equivalent dose in 2 Gy fractions (EQD₂) using the linear–quadratic model (α/β = 2). Results: Median follow-up was 10.3 months. Forty lesions (65%) were cervicothoracic and 21 (35%) were lumbosacral. One- and two-year overall survival (OS) were 45% and 29%, respectively, and one- and two-year local control (LC) were 89% and 88%, respectively. Gastrointestinal primary tumors were associated with inferior LC (HR 2.41, 95% CI 1.11–5.23, p = 0.026). Fifteen patients (27%) reported myelitis/neuropathic symptoms during follow-up; four (7%) developed new post-radiation myelitis or neuropathy (RMN) without radiologic progression. Five patients (9%) developed vertebral compression fractures (VCF). Cumulative EQD₂ was not significantly associated with RMN (p = 0.344); all affected patients had thecal sac EQD₂ > 95.5 Gy and relevant nerve roots EQD₂ > 108 Gy. Conclusions: ReSBRT provided a favorable LC with acceptable toxicity. High cumulative dose to the thecal sac and nerve roots may contribute to neurologic toxicity as peripheral nerve injury. Full article

This study investigates the influence of fiber bridging on the interlaminar strength of carbon fiber-reinforced polymer (CFRP) made from recycled carbon staple fiber yarn (rCF), compared to CFRP made from new fibers (vCF). Double-cantilever beam (DCB) tests measure the resistance of both materials against crack formation and the corresponding energy release rate (ERR). Several microscopic tools (SEM, CT) were then used to analyze the fracture surfaces and characterize the underlying failure mechanisms of the fiber bridges. The resulting ERR of rCFRP is four times (2140 J/m² compared to 587 J/m²) higher than that of vCFRP. SEM images of the fracture surface reveal that the fracture mechanism is fiber debonding followed by fiber pull-out with constant friction. This finding is confirmed by calculating the fiber bridging stress using the mathematical formulation of this effect resulting in a fiber bridge tension of approximately 70 N/mm². The main reason for the increased ERR of rCFRP compared to vCFRP is the extensive occurrence of fiber bridges in rCFRP due to the inhomogeneity of the rCF roving. This results in a pronounced nesting effect between adjacent rCF layers. The influence of the nesting effect on the ERR was investigated by testing samples with an increased layer orientation difference of 3° and 5°. This results in an ERR decrease of 26% in rCF and 30% in vCF. The nesting effect can be eliminated in vCFRP, but in rCFRP higher layer orientation, nesting is still visible. This finding suggests that the coarse, inhomogeneous structure of the rCFRP roving causes nesting regardless of the layer orientation and leads to a pronounced tendency to form fiber bridges. Full article

This paper proposes and experimentally evaluates a multi-level CPU-oriented execution method for high-throughput portion-based processing of file-backed Variant Call Format (VCF) data and automated mutation classification. The approach is based on a formally defined local processing scheme and integrates three coordinated levels of parallelism: block-based partitioning of file-backed VCF portions read sequentially into localized fragments with data-level parallel processing; task-level decomposition of feature construction into independent transformations; and execution-level specialization via JIT compilation of numerical kernels. To prevent performance degradation caused by nested parallelism, a resource-control mechanism is introduced as an execution rule that bounds effective parallelism and mitigates oversubscription, improving throughput stability on a single multi-core CPU node. Experiments on a public chromosome-17 VCF dataset for BRCA1-region pathogenicity classification demonstrate that the proposed multi-level local CPU execution (parsing/filtering, feature construction, and JIT-specialized numeric kernels) reduces runtime from 291.25 s (sequential) to 73.82 s, yielding a 3.95× speedup. When combined with resource-coordinated parallel model training, the end-to-end runtime further decreases to 51.18 s, corresponding to a 5.69× speedup, while preserving classification quality (accuracy 0.8483, precision 0.8758, recall 0.8261, F1 0.8502). A stage-wise ablation analysis quantifies the contribution of each execution level and confirms consistent scaling under resource-bounded execution. Full article

Background/Objectives: Software is now core infrastructure in biomedical science, yet fragmented workflows across subfields hinder reproducibility and delay the translation of data into actionable decisions. There is a critical need for a cross-disciplinary synthesis to bridge these silos and establish a unified framework for software maturity. This narrative review addresses this gap by synthesizing representative software ecosystems across three major pillars: bioinformatics, molecular modeling/simulations, and epidemiology/public health. Methods: A narrative review of articles indexed in PubMed/NCBI, Web of Science, and Scopus between 2000 and 2025 was conducted. Domain-specific terms related to bioinformatics, molecular modeling, docking, molecular dynamics, epidemiology, public health, and workflow management were combined with software- and algorithm-focused keywords. Studies describing, validating, or applying documented tools with biomedical relevance were included. Results: Across domains, mature data standards and reference resources (e.g., FASTQ, BAM/CRAM, VCF, mzML), widely adopted platforms (e.g., BLAST+ (v2.16.0, NCBI, Bethesda, MD, USA), Bioconductor (v3.20, Bioconductor Foundation, Seattle, WA, USA), AutoDock Vina (v1.2.5, Scripps Research, La Jolla, CA, USA), GROMACS (v2024.3, GROMACS Team, Stockholm, Sweden), Epi Info (v7.2.6, CDC, Atlanta, GA, USA), QGIS (v3.40, QGIS.org, Gossau, Switzerland), and increasing use of workflow engines were identified. Software pipelines routinely transform molecular and surveillance data into interpretable features supporting hypothesis generation. Conclusions: Integrated, standards-based, and validated software pipelines can shorten the path from measurement to decision in biomedicine and public health. Future progress depends on reproducibility practices, benchmarking, user-centered design, portable implementations, and responsible deployment of machine learning. Full article

The method of deriving fractional-order differential equations using Riesz fractional-order calculus is a new breakthrough, and it is possible to use the inverse scattering transform (IST) to solve the analytical solutions of the derived equations. However, there are still relatively few examples of using discrete Riesz fractional (DRF) order calculations. This article focuses on using discrete Riesz fractional-order calculations to derive a variable-coefficient fractional integrable semi-discrete nonlinear Schrödinger (vcfISDNLS) equation. On the one hand, we derive the vcfISDNLS equation through dispersion relation (DR) and DRF order calculations. On the other hand, we obtain the explicit expressions of the one-soliton solution, two-soliton solution, and three-soliton solution of this equation without reflection potentials (RPs). By deriving and solving the equation and displaying the obtained soliton solutions, possible evidential support can be provided for control engineering, automotive engineering, image processing, and optical communication systems. Full article

Objectives: This study aimed to evaluate the efficacy and toxicity of stereotactic body radiotherapy (SBRT) for spinal metastases, focusing on pain control, local tumor control, and the incidence of vertebral compression fractures (VCF). Materials and Methods: We retrospectively analyzed 179 patients with 217 spinal metastatic lesions who underwent SBRT between July 2020 and April 2022. The prescribed doses for SBRT were 18 or 20 Gy for one fraction, ≥24 Gy for three fractions, ≥20 Gy for four fractions, and ≥25 Gy for five fractions. Patient-reported treatment response was evaluated 1–3 months after SBRT completion. Local recurrence was defined as failure within the radiotherapy field. Pain response, local progression-free survival (LPFS), and the incidence of painful VCF were assessed. Prognostic factors for LPFS and VCF risk factors were evaluated. Results: The overall pain response rate was 80.8%. LPFS rates were 90.6% at 1 year and 83.0% at 2 years. Lytic/mixed lesions and involvement of multiple segments were significant prognostic factors for reduced LPFS. The cumulative incidence of painful VCF was 8.7% at 1 year and 12.8% at 2 years. A biologically effective dose (BED₃) ≥104 Gy was the only significant risk factor for painful VCF. Conclusions: SBRT demonstrated high efficacy for pain and local tumor control in spinal metastases, with an acceptable VCF risk. Full article

The utility of bioresponsive multifunctional hydrogel compositions for biomedical applications is rapidly increasing due to the diverse array of biological stimuli that can profoundly alter physicochemical gel properties that benefit therapeutic interventions. The purpose of this research is to explore a bioresponsive hydrogel as a drug-free bioengineering concept to fortify the natural physical contraceptive barriers at the cervicovaginal junction. The results of this research demonstrate that a hydrogel comprising 4% (w/w) Carbopol^® 974P and 4% (w/w) polyvinylpyrrolidone (CP4%/PVP4%) undergoes bioresponsive structural changes in the presence of simulated seminal fluid, pH 7.7, (SFS) that increases the work required to spread the gel under physiologically relevant vaginal conditions. Combination of this bioresponsive hydrogel with liquified human semen at a volumetric ratio of 1:5 dramatically reduces in vitro sperm migration by 97%. Simultaneously, total sperm motility decreases from 72.0 ± 9.9% to 7.9 ± 13.7%, which is significantly below the WHO criteria defined for male fertility. Safety assessments performed in vitro and in vivo underline a robust vaginal safety profile comparable to approved vaginal products. Moreover, the results from an exploratory animal study performed with female New Zealand White rabbits suggest that the drug-free physical barrier established intravaginally after exposure of the bioresponsive CP4%/PVP4% hydrogel to alkaline semen seems at least equivalent in the prevention of pregnancy in vivo to the VCF^® Gel (Apothecus Pharmaceuticals, Ronkonkoma, NY, USA), a marketed spermicidal on-demand product containing nonoxynol-9. Full article

Background: The genomic era has transformed not only the tools of medicine but the very logic by which we understand health and disease. Whole Exome Sequencing (WES), Clinical Exome Sequencing (CES), and Whole Genome Sequencing (WGS) have catalyzed a shift from Mendelian simplicity to polygenic complexity, from genetic determinism to probabilistic interpretation. This epistemological evolution calls into question long-standing notions of causality, certainty, and identity in clinical genomics. Yet, as the promise of precision medicine grows, so too do the tensions it generates: fragmented data, interpretative opacity, and the ethical puzzles of Variants of Uncertain Significance (VUSs) and unsolicited secondary findings. Results: Despite technological refinement, the diagnostic yield of Next-Generation Sequencing (NGS) remains inconsistent, hindered by the inherent intricacy of gene–environment interactions and constrained by rigid classificatory systems like OMIM and HPO. VUSs (neither definitively benign nor pathogenic) occupy a liminal space that resists closure, burdening both patients and clinicians with uncertainty. Meanwhile, secondary findings, though potentially life-altering, challenge the boundaries of consent, privacy, and responsibility. In both adult and pediatric contexts, genomic knowledge reshapes notions of autonomy, risk, and even personhood. Conclusions: Genomic medicine has to develop into a flexible, morally sensitive paradigm that neither celebrates certainty nor ignores ambiguity. Open infrastructures, dynamic variant reclassification, and a renewed focus on interdisciplinary and humanistic approaches are essential. Only by embracing the uncertainty intrinsic to our biology can precision medicine fulfill its promise, not as a deterministic science, but as a nuanced dialogue between genes, environments, and lived experience. Full article

Recently, environmental issues have compelled people worldwide to pursue sustainability and adopt circular economy practices across all engineering sectors, including polymer engineering and composite fabrication. A transition towards fabric-reinforced thermoplastics (FRTPs), a greener solution, has been recommended in recent years. On the other hand, utilizing recovered reinforcing phases, such as recycled carbon fiber (rCF), has attracted tremendous attention. In this framework, the aim of this research is to investigate the performance of acrylic-based FRTPs (Elium^® resin developed by Arkema). Woven virgin carbon fiber (vCF) and non-woven recycled carbon fiber (rCF) fabrics were used as reinforcement architectures for the fabrication of composites via resin infusion. The optimized formulation selected for the matrix showed flexural modulus and flexural strength of 5 GPa and 78 MPa, respectively. Composites prepared with woven vCF reached 36 GPa and 620 MPa values of flexural modulus and strength, respectively. The study of non-woven fabric is of particular interest, because the web is composed of recycled carbon fibers obtained from end-of-life (EoL) thermoset composite components. The results were promising; the flexural modulus reached 8 GPa, and the flexural strength was 113 MPa. Improvements are anticipated, especially in the parameters and conditions of the molding process. Full article

Background/Objectives: Vitamin C is frequently used in several dietary supplements due to its proposed health-promoting properties, while phenolic compounds and especially flavonoids have been suggested to provide synergistic antioxidant and cardiovascular benefits. However, the specific interactions between these compounds and their individual contributions to biological activity remain underexplored. This study aimed to evaluate the antioxidant potential and anti-inflammatory and antiplatelet biological effects of a high-dose (1 g) vitamin C–low-dose (50 mg) bioflavonoid (VCF)-based supplement using both in vitro and in vivo approaches in human platelets. Methods: Total phenolic content was quantified and antioxidant capacity was assessed using DPPH, FRAP, and ABTS assays and compared to individual phenolic standard compounds, including (simple phenolics like gallic acid, flavonoids like quercetin and catechin, and polyphenols like curcumin and tannin), and a standard supplement containing only high-dose vitamin C (VC). ATR-FTIR spectroscopy was used to assess molecular interactions between vitamin C and flavonoids. In vitro anti-inflammatory and antiplatelet activities of all supplements and standards were assessed by quantifying their IC₅₀ values against ADP, PAF, and thrombin-induced platelet aggregation. The in vivo evaluation of the efficacy and synergy of VCF supplement versus VC was achieved by a two-arm clinical study in healthy volunteers by quantifying their platelet reactivity, which was measured via EC₅₀ values on the aforementioned platelet agonists (PAF, ADP, and Thrombin) before (t = 0) and after receiving either solely VC or VCF supplementation for four weeks. Results: From all phenolic standards, the flavonoids and especially a mixture of flavonoids (catechin + quercetin) showed higher in vitro antioxidant capacity and anti-inflammatory and antiplatelet efficacy, followed by polyphenols and then simple phenolics. The VCF supplement showed the most potent antioxidant capacity, but also the strongest anti-inflammatory and antiplatelet activities too, in comparison to the VC and the mixture of flavonoids, suggesting higher synergy and thus bio-efficacy as a result of the co-presence of flavonoids and vitamin C in this supplement. Platelet reactivity decreased over time for PAF and thrombin in both arms of the trial, but no significant differences were observed between treatment groups, suggesting that the number of flavonoids used was not sufficient to translate the in vitro findings to the in vivo setting. Conclusions: VC-containing supplements provide antioxidant, anti-inflammatory, and antiplatelet benefits, while the incorporation of flavonoids may provide synergistic health benefits, but more in vivo assessment is needed to fully evaluate the dose efficacy. Full article

The degree of anisotropy and heterogeneity in coarse-grained materials significantly affects ultrasonic propagation behavior and scattering. This paper proposes a vector coherent factor threshold total focusing imaging method (VCF-T-TFM) for austenitic stainless steel, based on material properties, through a combination of simulation and experimentation. Three types of austenitic stainless steel weld test blocks with varying degrees of heterogeneity were selected containing multiple side-drilled hole defects, each with a diameter of 2 mm. Full-matrix data were collected using a 32-element phased array probe with a center frequency of 5 MHz. The grain size and orientation of the material were quantitatively observed via electron backscatter diffraction (EBSD). By combining the instantaneous phase distribution of the TFM image, the coarse-grained material coherence compensation value (C_A) and probability threshold (P_T) were optimized for different heterogeneous regions, and the vector coherence imaging threshold (γ) was adjusted. The defect imaging results of homogeneous material (carbon steel) and three austenitic stainless steels with different levels of heterogeneity were compared, and the influence of coarse-grained, anisotropic heterogeneous structures on the imaging signal-to-noise ratio was analyzed. The results show that the VCF-T-TFM, which considers the influence of material properties on phase coherence, can suppress structural noise. Compared to compensation results that did not account for material properties, the signal-to-noise ratio was improved by 97.3%. Full article

Background/Objectives: The objective of this study was to clinically validate the performance of the Nanox.AI HealthOST software in detecting incidental vertebral compression fractures (VCFs) on outpatient chest and abdomen CT scans using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A secondary aim was to assess the rate of missed VCFs using initial radiologist reports. Methods: A retrospective analysis was performed on 590 outpatient CT scans. HealthOST, an artificial intelligence solution from Nanox.AI that allows for automated spine analysis using CT images was evaluated against a consensus ground truth established by two radiologists, including a senior musculoskeletal radiologist. Two vertebral body height reduction thresholds were tested: mild (>20%) and moderate (>25%). Original radiologist reports were reviewed to identify missed VCFs. Results: At the 20% threshold, the AI achieved a sensitivity of 92.0%, a specificity of 52.7%, a PPV of 16.5%, and an NPV of 98.5%. At the 25% threshold, sensitivity decreased to 78.0%, while specificity improved to 94.2%, with a PPV of 51.1% and an NPV of 98.2%. The AI identified 88% and 92% of fractures missed by radiologists at the 20% and 25% thresholds, respectively. Conclusions: The Nanox HealthOST AI solution demonstrates potential as an effective screening tool, with threshold selection adaptable to clinical needs with a secondary review by a radiologist that is advisable to ensure diagnostic accuracy. The study further indicates that radiologists often overlook VCFs in reporting non-indicated cases and that AI has a role in enhancing the detection and reporting of vertebral compression fractures in routine clinical practice. Full article

Introduction: Vertebral Compression Fractures (VCF) are the most common vertebral fractures, usually osteoporotic, with rising incidence. The natural history of VCFs-related pain remains unclear, and treatment protocols are still being evaluated, ranging from conservative to surgical. Patient-reported measures have been proven inaccurate and carry significant biases. This study examines maximal tenderness location (MTL) to palpation and percussion on physical examination during VCF healing and the postoperative period. Methods: A prospective study included 40 patients treated for VCFs per the NICE guidelines (2013) from 2019 to 2021. Treatment was either conservative (n = 12) or surgical (n − 28), Balloon Kyphoplasty (BKP). All patients’ MTL were recorded in EMR (Electronic Medical Record) on every visit. BKP was offered for severe ongoing pain after a recent, unhealed vertebral fracture despite optimal pain management, progressive fracture collapse, or lack of union. Follow-up was six months. Pain evolution was analyzed using Kaplan–Meier survival curves, Log-Rank tests, Mann–Whitney U tests, t-tests, and logistic regression models. A p-value < 0.05 was considered statistically significant. Results: 12 patients were treated conservatively, and 28 underwent BKP for T12-L2 VCFs, accounting for 75% of fractures, mostly single-level fractures. All initially suffered MTL over the VCF; BKP patients showed local VCF pain resolution after 3.5 weeks following surgery while lasting seven weeks under conservative treatment. Lumbosacral pain was more prevalent following BKP (OR = 4, p = 0.05) and developed earlier. Conclusions: This study is novel in relating physical examination findings to fracture age and treatment provided, suggesting that VCFs-related pain is a time-related shift from local fracture pain to lumbosacral pain. Patient-reported pain scales may not reliably distinguish between these varying pain patterns. These findings suggest that only local VCF pain should be considered for surgical treatment. Future studies evaluating VCF outcomes should address physical examination and not rely solely on patient-reported metrics. Full article

Background: Navify^® Mutation Profiler (Navify MP) is a cloud-based, tertiary analysis software that provides curation, annotation, and reporting of somatic genomic alterations and biomarker signatures identified by next-generation sequencing. The Navify MP software leverages Association for Molecular Pathology/American Society of Clinical Oncology/College of American Pathologists (AMP/ASCO/CAP) Somatic Variant Classification Guidelines to provide information on detected somatic genomic variants and associated therapies according to region-specific approvals. Methods: This validation study assessed the accuracy of the Navify MP software and curation process for hematologic malignancies as compared to expert opinion. A total of 86 variants derived from hematologic malignancies (including myeloid and lymphoid leukemias, B cell lymphomas, and multiple myeloma) were used to contrive 12 VCF files. The VCFs were made up of the following classes of genomic alterations: single nucleotide variants, small insertions and deletions, fusions, and copy number alterations. Of the 86 variants, 42 were Tier IA, and 44 were non-Tier IA, based on AMP/ASCO/CAP classification. The study was performed at four sites with seven software users (molecular genetics experts). Results: Tier classification agreement between Navify MP and expert user assignment was 91.34% for Tier IA and 95.02% across all hematologic variants. The agreement on associated therapies for the Navify MP-classified Tier IA hematologic variants was 99.08%. Conclusions: Navify MP is a robust automated solution for genomic variant reporting of hematologic malignancies and remains up to date with evolving regional approvals and medical guidelines. Full article